Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free system
Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free system
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DOI：
10.1074/jbc.273.43.28378
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发表时间：
1998-10-23
影响因子：
4.8
通讯作者：
Fisher, DE
中科院分区：
文献类型：
--
作者：
Ding, HF;McGill, G;Fisher, DE
p53在癌症治疗中调节细胞凋亡的机制尚不完全清楚。在这里，无细胞提取物从辐射的肿瘤细胞中，内源性p53蛋白被证明参与半胱天冬酶激活。这种凋亡活性也是癌基因依赖性的，但一般不依赖于转录或Bax或细胞色素c的存在。该系统的一般用途是作为细胞凋亡调节剂的无细胞筛选。以这种方式，蛋白激酶A的深刻影响被确定和证实，在体内由cAMP对p53依赖性细胞凋亡的不同触发器的保护。该系统提供了直接的生化证据，p53蛋白可以通过蛋白质-蛋白质相互作用抑制凋亡信号，并揭示了一个能够调节p53依赖性半胱天冬酶激活的调节激酶通路。
The mechanism by which p53 modulates apoptosis in cancer therapy is incompletely understood. Here, cell-free extracts from irradiated tumor cells are described in which endogenous p53 protein is shown to participate in caspase activation. This apoptotic activity is also oncogene dependent, but independent of transcription in general or the presence of Bax or cytochrome c. A general use for this system is as a cell-free screen for apoptosis modulators. In this way, profound effects of protein kinase A were identified and corroborated in vivo by the protection conferred by cAMP against diverse triggers of p53-dependent apoptosis, This system provides direct biochemical evidence that p53 protein can transduce apoptotic signals through protein-protein interactions and reveals a modulator kinase pathway capable of regulating p53-dependent caspase activation.